Die Rolle von Plazebos in der Kopfschmerzforschung

Zusammenfassung

Die Wirkung von Medikamenten oder nicht medikamentöser Therapie zur Behandlung von Kopfschmerzen kann nur durch die Durchführung von plazebokontrollierten Studien wissenschaftlich belegt werden. Um diese Studien wissenschaftlich sauber durchführen zu können, müssen die Einflussfaktoren bekannt sein, welche den Plazeboeffekt beeinflussen. Dazu gehören beispielsweise die Erwartungshaltung der Patienten, die Applikationsform des Plazebos (als Tablette oder Injektion) und die unterschiedliche Häufigkeit der Plazeboeinnahme als Akuttherapie sowie die prophylaktische Therapie der Kopfschmerzen. Nur wenn diese Einflussvariablen bekannt sind können optimale Studiendesigns entworfen und umgesetzt werden.

Abstract

The only way to appreciate the efficacy of drug and behavioural therapy in the treatment of headache is to perform placebo-controlled, randomised trials. In order to plan and conduct these studies in the most appropriate way any factors influencing the placebo response have to be known. This paper reviews these factors, for example, expectations and applications of placebo. Response rates to placebo in the treatment of acute headache episodes and headache prophylaxis and factors influencing those are reported. These variables have to be known to properly calculate the power of planned randomised trials.

Literatur

• 1 Levine J D, Gordon N C, Fields H L. The mechanism of placebo analgesia.  Lancet. 1978;  2 654-657
• 2 Petrovic P, Kalso E, Petersson K M. et al . Placebo and opioid analgesia - imaging a shared neuronal network.  Science. 2002;  295 1737-1740
• 3 Benedetti F. Placebo and endogenous mechanisms of analgesia.  Handb Exp Pharmacol. 2007;  177 393-413
• 4 Benedetti F, Mayberg H S, Wager T D. et al . Neurobiological mechanisms of the placebo effect.  J Neurosci. 2005;  25 10390-10402
• 5 Benedetti F, Rainero I, Pollo A. New insights into placebo analgesia.  Curr Opin Anaesthesiol. 2003;  16 515-519
• 6 Tfelt-Hansen P. Methodology of treatment trials for acute migraine attacks. In: Olesen J, Tfelt-Hansen P (eds) Headache Treatment: Trial Methodology and New Drugs. Philadelphia; Lippincott-Raven 1997: 111-117
• 7 Tfelt-Hansen P, Henry P, Mulder L J. et al . The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine.  Lancet. 1995;  346 923-926
• 8 Henry P, Hiesseprovost O, Dillenschneider A. et al . Efficacy and tolerance of effervescent aspirin metoclopramide association in the treatment of migraine attack.  Presse Med. 1995;  24 254-258
• 9 Diener H C. for the ASASUMAMIG Study Group . Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study.  Cephalalgia. 1999;  19 581-588
• 10 Bendtsen L, Mattsson P, Zwart J A. et al . Placebo response in clinical randomized trials of analgesics in migraine.  Cephalalgia. 2003;  23 487-490
• 11 Tfelt-Hansen P, Block G. et al, International Headache Society Clinical Trials Subcommitee . Guidelines for controlled trials of drugs in migraine: second edition.  Cephalalgia. 2000;  20 765-786
• 12 Ferrari M D, Roon K I, Lipton R B. et al . Oral triptans (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials.  Lancet. 2001;  358 1668-1675
• 13 Holroyd K A, Penzien D B, Cordingley G E. Propranolol in the management of recurrent migraine: a meta-analytic review.  Headache. 1991;  31 333-340
• 14 Mathew N T, Saper J R, Silberstein S D. et al . Migraine prophylaxis with divalproex.  Arch Neurol. 1995;  52 281-286
• 15 Peikert A, Wilimzig C, Köhne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study.  Cephalalgia. 1996;  16 257-263
• 16 Klapper J. on behalf of the Divalproex Sodium in Migraine Prophylaxis Study Group . Divalproex sodium in migraine prophylaxis: a dose-controlled study.  Cephalalgia. 1997;  17 103-108
• 17 Ven L LM van de, Franke C L, Koehler P J. et al . Prophylactic treatment of migraine with bisoprolol: a placebo-controlled study.  Cephalalgia. 1997;  17 596-599
• 18 Diener H C, Foh M, Iaccarino C. et al . Cyclandelate in the prophylaxis of migraine: a randomised parallel, double-blind study in comparison with placebo and propranolol.  Cephalalgia. 1996;  16 441-447
• 19 Diener H C, Kronfeld K, Boewing G. et al . Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial.  Lancet Neurol. 2006;  5 310-316
• 20 Linde K, Streng A, Jurgens S. et al . Acupuncture for patients with migraine: a randomized controlled trial.  JAMA. 2005;  293 2118-2125
• 21 Craen A JM de, Tijssen J GP, Gans J de. et al . Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos.  J Neurol. 2000;  247 183-188
• 22 Bausell R B, Lao L, Bergman S. et al . Is acupuncture analgesia an expectancy effect? Preliminary evidence based on participants' perceived assignments in two placebo-controlled trials.  Eval Health Prof. 2005;  28 9-26
• 23 Geraud G, Olesen J, Pfaffenrath V. et al . Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design.  Cephalalgia. 2000;  20 30-38
• 24 Diener H C, Tfelt-Hansen P, Dahlöf C. et al . Topiramate in migraine prophylaxis: results from a placebo-controlled trial with propranolol as an active control.  J Neurol. 2004;  251 943-950
• 25 Brandes J, Saper J, Diamond M. et al . Topiramate for migraine prevention: a randomized controlled trial.  JAMA. 2004;  291 965-973
• 26 Bussone G, Diener H, Pfeil J. et al . Topiramate 100 mg/day in migraine prevention: a pooled analysis of double-blind randomised controlled trials.  Int J Clin Pract. 2005;  59 961-968
• 27 Silberstein S D, Neto W, Schmitt J. et al . Topiramate in migraine prevention: results of a large controlled trial.  Arch Neurol. 2004;  61 490-495
• 28 Silberstein S D, Gobel H, Jensen R. et al . Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: a multicentre, double-blind, randomized, placebo-controlled, parallel-group study.  Cephalalgia. 2006;  26 790-800
• 29 Mathew N T, Frishberg B M, Gawel M. et al . Botulinum toxin type A (BOTOX) for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial.  Headache. 2005;  45 293-307
• 30 Diener H, Bussone G, Oene J Van. et al .Topiramate reduces headache days in chronic migraine: A randomized, double-blind, placebo-controlled study. Cephalalgia 2007, in press
• 31 Silvestrini M, Bartolini M, Coccia M. et al . Topiramate in the treatment of chronic migraine.  Cephalalgia. 2003;  23 820-824
• 32 Mathew N, Hettiarachchi J, Alderman J. Tolerability and safety of eletriptan in the treatment of migraine: a comprehensive review.  Headache. 2003;  43 962-974
• 33 Diener H. Eletriptan in migraine.  Exp Rev Neurotherapeutics. 2005;  5 43-54
• 34 Goadsby P J, Lipton R B. Newer triptans: emphasis on rizatriptan.  Neurology. 2000;  55 S1-S2
• 35 Diener H C. persönl. Mitteilung. 
• 36 Loder E, Goldstein R, Biondi D. Placebo effects in oral triptan trials: the scientific and ethical rationale for continued use of placebo controls.  Cephalalgia. 2005;  25 124-131
• 37 Lewis D, Ashwal S, Hershey A. et al . Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society.  Neurology. 2004;  63 2215-2224
• 38 Visser W H, Winner P, Strohmaier K. et al . Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies.  Headache. 2004;  44 891-899
• 39 Winner P, Lewis D, Visser H. et al . Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized, double-blind, placebo-controlled study.  Headache. 2002;  42 49-55
• 40 Geraud G, Lanteri-Minet M, Lucas C. et al . French guidelines for the diagnosis and management of migraine in adults and children.  Clin Ther. 2004;  26 1305-1318
• 41 Ahonen K, Hamalainen M L, Eerola M. et al . A randomized trial of rizatriptan in migraine attacks in children.  Neurology. 2006;  67 1135-1140
• 42 Lewis S W, Winner P, Wasiewski W. The placebo responder rate in children and adolescents.  Headache. 2005;  45 232-239
• 43 Ekbom K, Monstad I, Prusinski A. et al . Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study.  Acta Neurol Scand. 1993;  88 63-69
• 44 Nilsson Rehmanl A IM, Laudon Meyer E L, Cordonnier C. et al . Placebo response in cluster headache trials: a review.  Cephalalgia. 2003;  23 504-510
• 45 Diener H, Matias-Guiu J, Hartung E. et al . Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily.  Cephalalgia. 2002;  22 209-221
• 46 Reuter U, Sanchez Del Rio M, Carpay J. et al . Placebo adverse events in headache trials: headache as an adverse event of placebo.  Cephalalgia. 2003;  23 496-503
• 47 Gauler T C, Weihrauch T R. Placebo. München, Wien, Baltimore; Urban & Schwarzenberg 1997
• 48 Diener H C, Hartung E, Chrubasik J. et al . A comparative study of acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomised, controlled, double-blind, parallel group phase III study.  Cephalalgia. 2001;  21 140-144